Background and Objective: Negative feedback is common in biological processes and can increase a systems stability to internal and external perturbations.The homeostasis is one of the five most important core physiological principles.We hypothesize that there may be function-specific homeostasis, a negative feedback response for a function to be perfectly performed.The proliferation-specific homeostasis (PlSH) of PC 12 cells was studied in this paper.Study Design/Materials and Methods: The PC12 cells were subjected to temperature at 30, 35,37 and 40 ℃, glucose at 0, 15, 20, 22, 24, 26, 28, 30, 50, 70, 72, 74, 76, 80 and 90 mM, glutamine at 0, l, 2, 4 and 10 mM, and nucleotide at 0, 10, 20 25, 30, 40,50 and 500 nM in Roswell Park Memorial Institute 1640 (RPMI1640) medium, respectively.The ratio of nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH,NAD+/NADH, and the protein level of sirtuin 1 (SIRT1) were assessed using NAD(H) recycling assay and Western blotting, respectively, after the 12 h cultivation.The proliferation was examined using 5-bromodeoxyuridine (BrdU)after the 48 h cultivation.Results: Among the studied media, PC12 cells subjected to temperature at 37 ℃, glucose at 26~70 mM, glutamine at 1 and 2 mM and nucleotide at 30 and 40 nM in RPMI-1640 medium proliferated at maximum rate, respectively.The minimum of NAD+/NADH and SIRT1 level of the PC12 cells was at 35 and 37 ℃ for temperature, at 10 mM for glucose at 10, 20, 30, 70 and 90 mM, at 2 mM for glutamine, and at 30 nM for nucleotide, respectively.Conclusions: There may be a P1SH which may use NAD+/NADH and then SIRT1 to maintain the optimum proliferation rate and resist against the medium change.